This invention lies in the field of glues designed for surgical or therapeutic use.
More precisely, this invention deals with a glue comprising a mixture of collagen and a crosslinking agent of the aldehyde type or a modified collagen with aldehyde functions and presented in lyophilised form. It also concerns a process for preparing such glue, its applications, the combination of this glue with a prosthetic material to obtain adhesive prostheses and the method for preparing said prostheses.
This glue is particularly suited to gluing two biological tissues together or to glue a prosthesis onto a biological tissue. It can also be applied directly to a biological tissue. In this latter case, it may notably be used as a local haemostatic device or a support for sustained-release drugs.
There are essentially two types of biological glues in the market: fibrin-based glues and collagen-based glues.
Fibrin-based glues, such as Tissucol, have been used since the 1970s. These glues contain a fibrinogen whose polymerisation is induced by a thrombin solution in the presence of factor XIII and fibronectin. This polymerisation leads to the formation of a fibrin clot that forms the bond. In fact, the aim is to recreate a coagulation phenomenon in situ. The problem related to these glues lies in the use of products made with human plasma, with the risks of contamination by viruses or related non-conventional transmissible agents.
Collagen is particularly well suited for use in glue as this biomaterial, capable of solidifying and then being reabsorbed, is biocompatible. Collagen as such, however, has weak adhesive power.
Thus, a composition based on collagen, resorcinol and formaldehyde was developed in the 1960s (GRF glue or French glue). Resorcinol is combined with formaldehyde to obtain collagen crosslinking and the formation of a solid polymer network. Problems of toxicity have been observed, mainly linked to the addition of formaldehyde (Braunwald et al., Surgery, 59: 1024-1030 (1966); Bachet et al., J Thorac. Cardiovasc. Surg., 83: 212-217 (1982)).
Document EP 0 862 468 describes the use of a macromolecular polyaldehyde, such as oxidized starch, for the crosslinking of a collagenic constituent in the context of biodegradable biological glues. It has been demonstrated that the mixture of such an aldehyde with a collagenic constituent, both in an aqueous solution or rehydrated after lyophilisation, is able to form an adhesive crosslinked material with no phenomenon of aldehyde diffusion.
In practice, however, it has been seen that the required system is complex and delicate to handle for the user. It requires:                means of storage and availability of two distinct compositions,        supply of these compositions in heated syringes,        their extemporaneous mixture using a specific system,        application of the mixture, as quickly as possible, on the wound to be treated.        
The result is that this type of glue is not practical to use.
Document EP 0 913 162 foresees the application of a support combined with collagen, for example a glutaraldehyde crosslinked bovine collagen, for the treatment of hernias. In this document, the bond is obtained by applying energy and pressure, the energy having the effect of creating free ends on the collagen fibres and the pressure or force creating new bonds between these ends and the polymer chains of the other surfaces involved.
In this last case, the product is directly ready for use and its storage is made easier. Obtaining the bonding effect, however, depends on the practitioner's application of a source of energy. This step requires the presence of a specific material and highly complicates the operating technique. In the end, it is not of great interest in terms of cost and time compared with the conventional fastening techniques (staples and sutures).
There is therefore an obvious need for biological glues and derived prostheses that are easy to prepare, store, transport and apply.